The research proposal described in this grant proposal is designed to investigate the importance of the peptide hormones calcitonin, gastrin, and parathyroid hormone in normal and disordered calcium and bone mineral metabolism. This will be accomplished by application of highly sensitive and specific radioimmunoassays which have been developed by the principal investigator for each of these hormones. In addition to these classical immunoassay methods, more sophisticated immunochemical procedures and newer radiometric techniques will be employed. The studies will be performed in both humans and a wide variety of animals. The wide and unique range of experimental subjects will result in a better understanding of the developmental and phylogenetic importance of these hormones. The secretion of these hormones will be evaluated both under basal conditions and during functional tests of secretion. The animal studies will provide appropriate experimental models for studying the secretion and the interrelationships of each of these hormones in physiological and pathophysiological states. The studies in humans will involve normal subjects as well as patients with disorders of calcium and skeletal homeostasis of all ages. The studies of hormonal metabolism and degradation will complement the in vivo studies. All of these studies should provide fundamental information about the secretion of parathyroid hormone, calcitonin and gastrin; the interrelationships among these hormones; and their role in abnormalities of bone mineral metabolism. This information should result in more effective and rational treatment of patients with disorders of calcium and skeletal homeostasis.